scholarly journals Pharmacokinetics of Hyperthermic Intrathoracic Chemotherapy following Pleurectomy and Decortication

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Paul H. Sugarbaker ◽  
O. Anthony Stuart ◽  
Christopher Eger
Keyword(s):  
Mitomycin C ◽  
Plasma Concentrations ◽  
Regional Chemotherapy ◽  
Hplc Assay ◽  
High Concentration ◽  
Direct Extension ◽  
Intrapleural Chemotherapy ◽  
Rapid Clearance ◽  
Pharmacokinetic Behavior ◽  
Pharmacologic Study

In patients with pseudomyxoma peritonei or peritoneal mesothelioma, direct extension of disease through the hemidiaphragm may result in an isolated progression of tumor within the pleural space. We monitored the intrapleural and plasma levels of mitomycin C and doxorubicin by HPLC assay in order to determine the pharmacokinetic behavior of this intracavitary use of chemotherapy. Our results showed a persistent high concentration of intrapleural drug as compared to plasma concentrations. The increased exposure for mitomycin C was 96, and the increased exposure for doxorubicin was 241. When the clearance of chemotherapy from the thoracic cavity was compared to clearance from the abdomen and pelvis, there was a considerably more rapid clearance from the abdomen as compared to the thorax. The pharmacologic study of intrapleural chemotherapy in these patients provides a strong pharmacologic rationale for regional chemotherapy in this group of patients.

The Importance of Exposure Time in Regional Chemotherapy: Mitomycin C and Fluoropyrimidines1

1988 ◽  
pp. 43-48 ◽  
Author(s):  
E. A. de Bruijn ◽  
P. H. Th. J. Slee ◽  
P. J. K. Kuppen ◽  
R. M. van der Hoeven ◽  
U. R. Tjaden ◽  
...  
Keyword(s):  
Mitomycin C ◽  
Exposure Time ◽  
Regional Chemotherapy

Abstract WP386: Acute Catecholamine Surge in Patients with Aneurysmal Subarachnoid Hemorrhage: Characteristics and Prognostic Value

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Koichi Uramaru ◽  
Yuichiro Kikkawa ◽  
Hiroki Sato ◽  
Taro Yanagawa ◽  
Kaima Suzuki ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Subarachnoid Hemorrhage ◽  
Acute Phase ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Demographic Data ◽  
Plasma Concentrations ◽  
Clinical Grade ◽  
High Concentration ◽  
Mutual Correlation ◽  
Inflammatory Reactions

Objectives: The characteristics of serum catecholamine concentration at the hyper-acute phase of aneurysmal subarachnoid hemorrhage (SAH) and its relationship between patient outcome and delayed vasospasm were investigated. Methods: Patients with aneurysmal SAH (170) were prospectively studied between August 2008 and June 2011. Baseline demographic data and physiological parameters, including plasma concentrations of adrenaline (AD), noradrenaline (NA) and dopamine (DP) were evaluated for all patients. Results: On admission, plasma AD, NA and DP levels were significantly higher in patients with a poor clinical grade on admission (Hunt & Kosnik: IV-V), compared to those with a good clinical grade on admission (Hunt & Kosnik: I-III). AD showed a markedly high concentration immediately after the onset of SAH and then rapidly decreased. NA levels peaked within 6 hours after onset, then significantly decreased. The increase of DP with time was not significant, but showed a similar trend to that of NA. The level of each catecholamine showed significant mutual correlation. Multivariate analyses demonstrated age, poor clinical grade, plasma AD and NA levels were predictors of poor patient outcome, and.poor clinical grade, Fisher scale and plasma AD level were predictors of the development of delayed vasospasm. Conclusions: The present findings suggest that sympathetic activation in patients in the acute phase of SAH reflects the severity of SAH, and is closely related to the development of delayed vasospasm, leading to the subsequent immune response and inflammatory reactions. Strategies for suppressing catecholamine at the hyperacute phase may contribute to vasospasm prevention and improve patient outcome.

CASE OF LIVER METASTASIS FROM COLON CANCER SUCCESSFULLY TREATED BY REGIONAL CHEMOTHERAPY WITH MITOMYCIN C ALONE

2002 ◽  
Vol 17 (2) ◽  
pp. 227-229
Author(s):  
Osamu Watanabe ◽  
Shunsuke Haga ◽  
Hiroyuki Kato ◽  
Toshinori Ooishi ◽  
Satoshi Kobayashi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Liver Metastasis ◽  
Mitomycin C ◽  
Regional Chemotherapy

scholarly journals Kinetic characterization of a saturable pathway for rapid clearance of circulating fibrin monomer

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 680-688
Author(s):  
BN Dardik ◽  
JR Shainoff
Keyword(s):  
Plasma Concentrations ◽  
Kinetic Mechanism ◽  
Soluble Form ◽  
Order Kinetic ◽  
Fibrinopeptide A ◽  
Extravascular Space ◽  
Fibrin Monomer ◽  
Aggregation Site ◽  
Rapid Clearance ◽  
Alpha Beta

The mechanism of clearance of circulating fibrin monomer was investigated in rabbits through (1) study of decay in plasma concentrations of 125I-labeled monomers with variant fibrinopeptide content and (2) concurrent analysis of decay of the monomers relative to coinjected 131I-fibrinogen. Under the conditions employed, essentially all of the fibrin became distributed in a soluble form in plasma and decayed independently of the coinjected fibrinogen. Among the species of fibrin studied, monomer lacking fibrinopeptide A alone (alpha-fibrin) underwent very rapid clearance by a saturable mechanism that was not evident in relatively sluggish clearance of monomer lacking either fibrinopeptide B alone (beta-fibrin) or both fibrinopeptides A and B (alpha beta-fibrin). Decay of alpha-fibrin conformed with a kinetic mechanism involving first-order permeation of the fibrin into extravascular space at a rate equivalent to that of permeation of fibrinogen; unlike fibrinogen, however, the alpha-fibrin underwent immediate absorption in parallel with permeation (t1/2 = 2.6 hours) at doses below an apparent saturating level of 3 mg/kg. At doses near the absorptive limit, the uptake accompanying permeation diminished as in a second-order kinetic mechanism, and at very high doses the plasma decay of the alpha-fibrin approached that of fibrinogen. The beta- and alpha beta-fibrins also permeated extravascular space in parallel with fibrinogen, but absorption proceeded sluggishly (t1/2 = 11 and 16 hours, respectively) at low doses and did not change with increasing dose. The uniquely rapid and saturable clearance of alpha-fibrin is suggested to involve uptake through the fibrin aggregation site that is blocked by fibrinopeptide A in fibrinogen and beta-fibrin and by tight binding to fibrinogen in soluble complexes formed by alpha beta-fibrin. A corollary of this hypothesis is that rapid uptake depends on dissociability of fibrin complexes for access to the aggregation site, a mechanism that is just the converse of uptake through aggregation.

scholarly journals Kinetic characterization of a saturable pathway for rapid clearance of circulating fibrin monomer

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 680-688 ◽  
Author(s):  
BN Dardik ◽  
JR Shainoff
Keyword(s):  
Plasma Concentrations ◽  
Kinetic Mechanism ◽  
Soluble Form ◽  
Order Kinetic ◽  
Fibrinopeptide A ◽  
Extravascular Space ◽  
Fibrin Monomer ◽  
Aggregation Site ◽  
Rapid Clearance ◽  
Alpha Beta

Abstract The mechanism of clearance of circulating fibrin monomer was investigated in rabbits through (1) study of decay in plasma concentrations of 125I-labeled monomers with variant fibrinopeptide content and (2) concurrent analysis of decay of the monomers relative to coinjected 131I-fibrinogen. Under the conditions employed, essentially all of the fibrin became distributed in a soluble form in plasma and decayed independently of the coinjected fibrinogen. Among the species of fibrin studied, monomer lacking fibrinopeptide A alone (alpha-fibrin) underwent very rapid clearance by a saturable mechanism that was not evident in relatively sluggish clearance of monomer lacking either fibrinopeptide B alone (beta-fibrin) or both fibrinopeptides A and B (alpha beta-fibrin). Decay of alpha-fibrin conformed with a kinetic mechanism involving first-order permeation of the fibrin into extravascular space at a rate equivalent to that of permeation of fibrinogen; unlike fibrinogen, however, the alpha-fibrin underwent immediate absorption in parallel with permeation (t1/2 = 2.6 hours) at doses below an apparent saturating level of 3 mg/kg. At doses near the absorptive limit, the uptake accompanying permeation diminished as in a second-order kinetic mechanism, and at very high doses the plasma decay of the alpha-fibrin approached that of fibrinogen. The beta- and alpha beta-fibrins also permeated extravascular space in parallel with fibrinogen, but absorption proceeded sluggishly (t1/2 = 11 and 16 hours, respectively) at low doses and did not change with increasing dose. The uniquely rapid and saturable clearance of alpha-fibrin is suggested to involve uptake through the fibrin aggregation site that is blocked by fibrinopeptide A in fibrinogen and beta-fibrin and by tight binding to fibrinogen in soluble complexes formed by alpha beta-fibrin. A corollary of this hypothesis is that rapid uptake depends on dissociability of fibrin complexes for access to the aggregation site, a mechanism that is just the converse of uptake through aggregation.

scholarly journals Congenital hyperinsulinism and Poland syndrome in association with 10p13–14 duplication

2017 ◽  
Vol 2017 ◽  
Author(s):  
Dinesh Giri ◽  
Prashant Patil ◽  
Rachel Hart ◽  
Mohammed Didi ◽  
Senthil Senniappan
Keyword(s):  
Plasma Concentrations ◽  
Pathogenic Mutation ◽  
High Plasma ◽  
Poland Syndrome ◽  
Congenital Hyperinsulinism ◽  
List Type ◽  
High Concentration ◽  
Chromosome 10 ◽  
Congenital Condition ◽  
Learning Points

Summary Poland syndrome (PS) is a rare congenital condition, affecting 1 in 30 000 live births worldwide, characterised by a unilateral absence of the sternal head of the pectoralis major and ipsilateral symbrachydactyly occasionally associated with abnormalities of musculoskeletal structures. A baby girl, born at 40 weeks’ gestation with birth weight of 3.33 kg (−0.55 SDS) had typical phenotypical features of PS. She had recurrent hypoglycaemic episodes early in life requiring high concentration of glucose and glucagon infusion. The diagnosis of congenital hyperinsulinism (CHI) was biochemically confirmed by inappropriately high plasma concentrations of insulin and C-peptide and low plasma free fatty acids and β-hydroxyl butyrate concentrations during hypoglycaemia. Sequencing of ABCC8, KCNJ11 and HNF4A did not show any pathogenic mutation. Microarray analysis revealed a novel duplication in the short arm of chromosome 10 at 10p13–14 region. This is the first reported case of CHI in association with PS and 10p duplication. We hypothesise that the HK1 located on the chromosome 10 encoding hexokinase-1 is possibly linked to the pathophysiology of CHI. Learning points: Congenital hyperinsulinism (CHI) is known to be associated with various syndromes. This is the first reported association of CHI and Poland syndrome (PS) with duplication in 10p13–14. A potential underlying genetic link between 10p13–14 duplication, PS and CHI is a possibility.

Interaction of the Antiarrhythmic Drug Procainamide with Phospholipid Bilayers

1995 ◽  
Vol 50 (3-4) ◽  
pp. 248-256 ◽  
Author(s):  
M. Suwalsky ◽  
F. Villena ◽  
M. Bagnara ◽  
C. P. Sotomayorc
Keyword(s):  
Sodium Channels ◽  
Antiarrhythmic Drugs ◽  
Plasma Concentrations ◽  
Phospholipid Bilayers ◽  
X Ray Diffraction ◽  
High Concentration ◽  
X Ray ◽  
Molecular Mechanism Of Action ◽  
Shape Changes

Several hypotheses link the molecular mechanism of action of the antiarrhythmic drugs (AAD) that belong to class I to non-specific interactions with phospholipids sited in the neighborhood of sodium channels in the membrane of the myocardium. Procainamide (PROC ), one of the least lipophilic drugs of this group, was induced to interact with bilayers of dimyristoylphosphatidylcholine (DMPC) and dimirystoylphosphatidylethanolamine (DMPE), liposomes of DMPC and human erythrocytes. The perturbing effects of PROC upon these systems were respectively determined by X-ray diffraction, fluorescence spectroscopy and scanning electron microscopy. It was found that PROC exerted very little effect upon DMPC and DMPE even at such a high concentration as 10 mᴍ . However, at therapeutical plasma concentrations, PROC induced shape changes in vitro to red cells.

Phase I clinical and pharmacokinetic study of leucovorin and infusional hepatic arterial fluorouracil.

1995 ◽  
Vol 13 (12) ◽  
pp. 2968-2972 ◽  
Author(s):  
D J Kerr ◽  
J A Ledermann ◽  
C S McArdle ◽  
J Buckels ◽  
J Neoptolemos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Plasma Concentrations ◽  
Hepatic Metastases ◽  
Hepatic Arterial Infusion ◽  
Maximum Tolerated Dose ◽  
Regional Chemotherapy ◽  
Pharmacokinetic Studies ◽  
Severe Diarrhea ◽  
Drug Concentrations

PURPOSE A phase I and pharmacokinetic trial was performed between October 1993 and June 1994 to determine the maximum-tolerated dose of hepatic arterial infusion (HAI) of fluorouracil (5-FU) and intravenous (IV) leucovorin (folinic acid; FA) in patients with hepatic metastases from colorectal cancer. PATIENTS AND METHODS Forty-three patients received 310 courses of HAI chemotherapy administered over 48 hours every 2 weeks. The regimen consisted of FA 200 mg/m2 by IV infusion over 2 hours, followed by a loading dose of 5-FU 400 mg/m2 by HAI over 15 minutes, followed by a 22-hour infusion of 5-FU at doses ranging from 0.8 to 1.84 g/m2, with identical chemotherapy on day 2. Pharmacokinetic studies were performed to determine peak and steady-state plasma concentrations (Css) of 5-FU. RESULTS Severe diarrhea and cardiac and neurologic toxicity were dose-limiting at 1.84 g/m2. The recommended dose for the 22-hour component of the schedule was 1.6 g/m2 and was associated with tolerable toxicity. A Css of 2.2 +/- 0.8 mumol/L for 5-FU was achieved on the recommended schedule, which compares favorably with conventional IV 5-FU regimens. Among 30 patients assessable for response, there were four complete responses and seven partial responses, and 12 patients with stable disease and seven with progressive disease, reported after 3 months (ie, six cycles) of therapy. CONCLUSION A regimen that combines 5-FU and FA has been identified for regional chemotherapy in patients with hepatic metastases from colorectal cancer. The systemic levels of 5-FU achieved are similar to the conventional IV de Gramont regimen using an identical schedule of 5-FU and FA, which implies that this chemotherapy has the best of both worlds, ie, a regional advantage in delivering high drug concentrations to the target organ with adequate systemic cover for extrahepatic micrometastases.

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